HGF/SF increases tumor blood volume: a novel tool for the in vivo functional molecular imaging of Met

Neoplasia. 2006 May;8(5):344-52. doi: 10.1593/neo.05685.

Abstract

Molecular functional and metabolic imaging allows visualization of disease-causing processes in living organisms. Here we present a new approach for the functional molecular imaging (FMI) of endogenous tyrosine kinase receptor activity using Met and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), as a model. HGF/SF and Met play significant roles in the biology and pathogenesis of a wide variety of cancers and, therefore, may serve as potential targets for cancer prognosis and therapy. We have previously shown that Met activation by HGF/SF increases oxygen consumption in vitro and results in substantial alteration of blood oxygenation levels in vivo, as measured by blood oxygenation level-dependent magnetic resonance imaging. Using contrast medium (CM) ultrasound imaging, we demonstrate here that HGF/SF induces an increase in tumor blood volume. This increase is evident in small vessels, including vessels that were not detected before HGF/SF treatment. The specificity of the effect was validated by its inhibition using anti-HGF/SF antibodies. This change in tumor hemodynamics, induced by HGF/SF and measured by CM ultrasound, is further used as a tool for Met FMI in tumors. This novel noninvasive molecular imaging technique may be applied for the in vivo diagnosis, prognosis, and therapy of Met-expressing tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Contrast Media / pharmacology
  • Diagnostic Imaging / methods*
  • Female
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms / blood supply
  • Neoplasms / pathology*
  • Neovascularization, Pathologic*
  • Oxygen / metabolism
  • Oxygen Consumption
  • Prognosis
  • Proto-Oncogene Proteins c-met / metabolism*

Substances

  • Contrast Media
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Oxygen